Role of PPAR-beta in hydrogen peroxide-induced apoptosis in human umbilical vein endothelial cells.
Peroxisome proliferator-activated receptor beta (PPAR-beta) is a ligand activated transcription factor belonging to the nuclear receptor superfamily. Recent evidence suggests that PPAR-beta has clearly defined roles in skin wound healing, inflammation and cell proliferation. However, little is known about the role of PPAR-beta in oxidative stress-induced apoptosis in human umbilical vein endothelial cells (HUVECs). In this study, a specific PPAR-beta ligand, L-165041, and antisense phosphorothioate oligodeoxynucleotides (asODNs) against PPAR-beta were used to reveal the role of PPAR-beta in oxidative stress-induced apoptosis. The results showed that H(2)O(2) at 0.5mM resulted in a marked increase of apoptosis and a significant down-regulation of PPAR-beta expression and activation in HUVECs. Moreover, L-165041 significantly inhibited H(2)O(2)-induced apoptosis (P<0.05) and asODNs against PPAR-beta markedly inhibited the de novo synthesis of PPAR-beta, which was accompanied by enhanced apoptosis induced by H(2)O(2) (P<0.05). These data demonstrated that H(2)O(2) down-regulated the expression and activation of PPAR-beta, which played important roles in H(2)O(2)-induced apoptosis in HUVECs.
Jiang
Bimei
B
Department of Pathophysiology, Xiangya School of Medicine, Central South University, Changsha, Hunan 410078, PR China.
Liang
Pengfei
P
Zhang
Bing
B
Song
Juan
J
Huang
Xiaoyuan
X
Xiao
Xianzhong
X
D017209:Apoptosis / Q000187:drug effects*; D001665:Binding Sites; D002478:Cells, Cultured; D004247:DNA / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D006861:Hydrogen Peroxide / Q000633:toxicity*; D020319:Oligodeoxyribonucleotides, Antisense / Q000378:metabolism; D016877:Oxidants / Q000633:toxicity*; D048068:PPAR-beta / Q000819:agonists / Q000235:genetics / Q000378:metabolism*; D010642:Phenoxyacetates / Q000494:pharmacology; D054735:Phosphorothioate Oligonucleotides / Q000378:metabolism; D013997:Time Factors; D014158:Transcription, Genetic / Q000187:drug effects; D014471:Umbilical Veins / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology
C520164:4-(3-(2-propyl-3-hydroxy-4-acetyl)phenoxy)propyloxyphenoxy acetic acid; D020319:Oligodeoxyribonucleotides, Antisense; D016877:Oxidants; D048068:PPAR-beta; D010642:Phenoxyacetates; D054735:Phosphorothioate Oligonucleotides; D004247:DNA; D006861:Hydrogen Peroxide